BR112023013640A2 - PLASMINE-RESISTANT PEPTIDES FOR IMPROVED THERAPEUTIC INDEX - Google Patents
PLASMINE-RESISTANT PEPTIDES FOR IMPROVED THERAPEUTIC INDEXInfo
- Publication number
- BR112023013640A2 BR112023013640A2 BR112023013640A BR112023013640A BR112023013640A2 BR 112023013640 A2 BR112023013640 A2 BR 112023013640A2 BR 112023013640 A BR112023013640 A BR 112023013640A BR 112023013640 A BR112023013640 A BR 112023013640A BR 112023013640 A2 BR112023013640 A2 BR 112023013640A2
- Authority
- BR
- Brazil
- Prior art keywords
- amino acids
- plasmin
- administration
- agents
- therapeutic index
- Prior art date
Links
- 102000004196 processed proteins & peptides Human genes 0.000 title abstract 2
- 108090000765 processed proteins & peptides Proteins 0.000 title abstract 2
- 231100001274 therapeutic index Toxicity 0.000 title abstract 2
- 150000008574 D-amino acids Chemical class 0.000 abstract 3
- 229940012957 plasmin Drugs 0.000 abstract 3
- 239000013543 active substance Substances 0.000 abstract 2
- PMHDSACGRKBACK-UHFFFAOYSA-N 4h-thieno[3,2-b]pyrrole-5-carboxylic acid Chemical compound S1C=CC2=C1C=C(C(=O)O)N2 PMHDSACGRKBACK-UHFFFAOYSA-N 0.000 abstract 1
- 208000017667 Chronic Disease Diseases 0.000 abstract 1
- 229940121734 D-amino-acid oxidase inhibitor Drugs 0.000 abstract 1
- 150000008575 L-amino acids Chemical group 0.000 abstract 1
- 206010029155 Nephropathy toxic Diseases 0.000 abstract 1
- 208000006011 Stroke Diseases 0.000 abstract 1
- 239000003795 chemical substances by application Substances 0.000 abstract 1
- 230000029087 digestion Effects 0.000 abstract 1
- XWQVQFBTSBCKLI-FKXNDIMNSA-N dnc008987 Chemical compound CC(C)[C@@H](C(O)=O)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H]([C@@H](C)CC)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCCNC(N)=N)NC(=O)CNC(=O)[C@@H](N)CC1=CC=C(O)C=C1 XWQVQFBTSBCKLI-FKXNDIMNSA-N 0.000 abstract 1
- 230000000694 effects Effects 0.000 abstract 1
- 239000003527 fibrinolytic agent Substances 0.000 abstract 1
- 238000001802 infusion Methods 0.000 abstract 1
- 238000007918 intramuscular administration Methods 0.000 abstract 1
- 238000001990 intravenous administration Methods 0.000 abstract 1
- 230000007694 nephrotoxicity Effects 0.000 abstract 1
- 231100000417 nephrotoxicity Toxicity 0.000 abstract 1
- 238000007920 subcutaneous administration Methods 0.000 abstract 1
- 229960000103 thrombolytic agent Drugs 0.000 abstract 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
- C07K7/04—Linear peptides containing only normal peptide links
- C07K7/06—Linear peptides containing only normal peptide links having 5 to 11 amino acids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/62—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being a protein, peptide or polyamino acid
- A61K47/64—Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/62—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being a protein, peptide or polyamino acid
- A61K47/64—Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent
- A61K47/645—Polycationic or polyanionic oligopeptides, polypeptides or polyamino acids, e.g. polylysine, polyarginine, polyglutamic acid or peptide TAT
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
- C07K7/04—Linear peptides containing only normal peptide links
- C07K7/08—Linear peptides containing only normal peptide links having 12 to 20 amino acids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/01—Fusion polypeptide containing a localisation/targetting motif
- C07K2319/10—Fusion polypeptide containing a localisation/targetting motif containing a tag for extracellular membrane crossing, e.g. TAT or VP22
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Organic Chemistry (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Molecular Biology (AREA)
- Epidemiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Genetics & Genomics (AREA)
- Biophysics (AREA)
- Biochemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Vascular Medicine (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Urology & Nephrology (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Immunology (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
peptídeos resistentes à plasmina para índice terapêutico melhorado. a invenção provê variantes de um agente ativo descrito anteriormente para o tratamento de acidente vascular cerebral, tat-nr2b9c, em que as características de ligação alvo são mantidas pela inclusão de l-aminoácidos no terminal c e a resistência à plasmina é conferida pela inclusão de d- aminoácidos. a nefrotoxicidade associada com d-aminoácidos pode ser reduzida pela inclusão de d-aminoácidos em um número mínimo de posições e/ou pela coadministração com um inibidor da d-aminoácido oxidase. os agentes ativos resultantes têm várias vantagens, incluindo administração ao mesmo tempo que agentes trombolíticos sem perda significativa de atividade devido à digestão de plasmina. os agentes resultantes também são mais adequados para administração por vias alternativas à infusão intravenosa, como subcutânea, intranasal e intramuscular, e para esquemas de administração múltipla para tratamento de condições crônicas.plasmin-resistant peptides for improved therapeutic index. The invention provides variants of a previously described active agent for the treatment of stroke, tat-nr2b9c, in which target binding characteristics are maintained by the inclusion of l-amino acids at the c-terminus and plasmin resistance is conferred by the inclusion of d- amino acids. nephrotoxicity associated with d-amino acids can be reduced by including d-amino acids at a minimum number of positions and/or by coadministration with a d-amino acid oxidase inhibitor. the resulting active agents have several advantages, including administration at the same time as thrombolytic agents without significant loss of activity due to plasmin digestion. the resulting agents are also better suited for administration by routes alternative to intravenous infusion, such as subcutaneous, intranasal, and intramuscular, and for multiple administration regimens for treating chronic conditions.
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US202163135498P | 2021-01-08 | 2021-01-08 | |
| US202163147711P | 2021-02-09 | 2021-02-09 | |
| US202163221874P | 2021-07-14 | 2021-07-14 | |
| PCT/US2022/011716 WO2022150655A1 (en) | 2021-01-08 | 2022-01-07 | Plasmin-resistant peptides for improved therapeutic index |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| BR112023013640A2 true BR112023013640A2 (en) | 2023-12-05 |
Family
ID=82357479
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| BR112023013640A BR112023013640A2 (en) | 2021-01-08 | 2022-01-07 | PLASMINE-RESISTANT PEPTIDES FOR IMPROVED THERAPEUTIC INDEX |
Country Status (9)
| Country | Link |
|---|---|
| EP (1) | EP4274596A1 (en) |
| JP (1) | JP2024502463A (en) |
| KR (1) | KR20230141958A (en) |
| AU (1) | AU2022206444A1 (en) |
| BR (1) | BR112023013640A2 (en) |
| CA (1) | CA3203688A1 (en) |
| IL (1) | IL304301A (en) |
| MX (1) | MX2023008086A (en) |
| WO (1) | WO2022150655A1 (en) |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6998106B1 (en) * | 1998-12-01 | 2006-02-14 | Duke University | Radioconjugation of internalizing antibodies |
| US7510824B2 (en) * | 1999-06-02 | 2009-03-31 | Nono Inc. | Method of screening peptides useful in treating traumatic injury to the brain or spinal cord |
-
2022
- 2022-01-07 BR BR112023013640A patent/BR112023013640A2/en unknown
- 2022-01-07 EP EP22737218.2A patent/EP4274596A1/en active Pending
- 2022-01-07 AU AU2022206444A patent/AU2022206444A1/en active Pending
- 2022-01-07 CA CA3203688A patent/CA3203688A1/en active Pending
- 2022-01-07 KR KR1020237026532A patent/KR20230141958A/en unknown
- 2022-01-07 MX MX2023008086A patent/MX2023008086A/en unknown
- 2022-01-07 WO PCT/US2022/011716 patent/WO2022150655A1/en active Application Filing
- 2022-01-07 JP JP2023541501A patent/JP2024502463A/en active Pending
-
2023
- 2023-07-06 IL IL304301A patent/IL304301A/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| JP2024502463A (en) | 2024-01-19 |
| EP4274596A1 (en) | 2023-11-15 |
| KR20230141958A (en) | 2023-10-10 |
| MX2023008086A (en) | 2023-08-01 |
| IL304301A (en) | 2023-09-01 |
| AU2022206444A1 (en) | 2023-07-20 |
| WO2022150655A1 (en) | 2022-07-14 |
| CA3203688A1 (en) | 2022-07-14 |
| AU2022206444A9 (en) | 2024-05-02 |
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